Adverse Drug Reactions Flashcards
What is an adverse drug reaction?
Any undesirable reaction that results in a detriment to the well being of the patient in any way, in the absence of another biologically plausible explanation
What groups are adverse drug reactions most common in?
Elderly or frail, multimorbid and polypharmacy
How is the therapeutic index calculated?
TD50/ED50
What are some drugs with a narrow therapeutic index and must be used with caution?
Index <2 = theophylline, warfarin, lithium, digoxin, gentamicin, vancomycin, cyclosporin, phenytoin, carbamazepine, levothyroxine
When may adverse reactions to a drug bet detected?
Drug development (pre-clinical) = most efficient, least attrition Clinical trials (phase1-3) = limited sample size, exclusion of frail patients Post-marketing surveillance (phase 4 onwards) = less efficient, highest attrition but most data available
What are the phases of drug metabolism?
Phase 1 = usually through Cyp P450, oxidation, reduction and hydrolysis
Phase 2 = conjugation, enables excretion in urine/bile
What phase of drug metabolism are almost all adverse reactions associated with?
Phase 1
What is the classification of adverse drug reactions?
Type A = augmented pharmacological effects Type B = bizarre effects (idiosyncratic) Type C = chronic effects Type D = delayed effects Type E = end of treatment effects Type F = failure of treatment
What is the difference between type A and type B drug reactions?
Type A is dose dependent and predictable
Type B is dose independent and unpredictable
What categories are type A reactions split into?
Pre-renal failure, renal failure and post-renal failure
Drug interactions
What are some features of type A pre-renal failure?
Hypovolaemia and hypotension
Drug causes include diuretics and ACE inhibitors/ARBs
What are some features of type A renal failure?
AIN/tubular necrosis
May be caused by gentamicin, sulphonamides or aspirin
What are some features of type A post-renal failure?
Retroperitoneal fibrosis, crystaluria and urinary calculi
May be due to use of methysergide or chemotherapy
What are the different types of drug interactions?
Drug-drug reactions
Drug-disease reactions
Drug-food reactions
What are some examples of some common drug-drug interactions?
Statins and macrolides
Clopidogrel and PPIs
Warfarin and many drugs
ACE inhibitors increase effects of sulphonylureas
What are some common herbal remedies that may cause drug-drug interactions?
Grapefruit juice (Cyp P450) for vitamin C Gingko biloba (anticoagulant) for dementia Saw palmetto (anticoagulant) for BPH Glucosamine (hyperglycaemia, anticoagulant) for OA
What are some common drug-disease interactions?
NSAIDs and COX-2 can exacerbate CHF
Urinary retention in BPH patients on decongestants
Constipation worsened by calcium channel blockers
Beta blockers and asthma
What are some examples of foods rich in K+?
Bananas, oranges, green leafy vegetables
Interact with ACE inhibitors, ARBs and K+ sparing diuretics
What are some examples of foods that can interact with warfarin?
Rich in vitamin E and K = apples, chickpeas, spinach, nuts, kiwi, broccoli
What are some foods that can alter pH to cause drug interactions?
Chicken, turkey, milk, soy, cheese, yogurt
Interact with antibiotics, thyroid medications, digoxin and diuretics
What are some foods that contain cytochrome P450?
Grapefruit, apple, orange, cranberry
Interact with statins and anti-histamines
What are some examples of type B reactions?
Drug rashes, bone marrow aplasia, hepatic necrosis = higher mortality
What causes type C reactions?
Due to prolonged therapy = can be anticipated but patient must be warned before starting therapy
What are some examples of type C reactions?
Steroids cause Cushing’s
Beta blockers cause diabetes
NSAIDs cause hypertension
When do type D reactions tend to occur?
Remote from treatment = usually many years after stopping
What are some features of type D reactions?
Devastating = teratogenic or carcinogenic effects
Less frequent now due to rigorous pre-clinical testing
What cause type E reactions?
Abrupt withdrawal of drug = causes rebound effects
What are the two mechanisms of type E reactions?
Loss of physiological coping = beta blocker withdrawal and angina
Mechanism-dependent biological activity = steroid withdrawal and Addisonian crisis
What can the black triangle status be applied to?
New medicines that have a new active ingredients
Biologics or vaccines
Licensing requirements
When can the black triangle status of a drug be reviewed?
After 2 years = only removed when safety is established
When is a yellow card filled in?
Legal requirement = must fill in when patient has an unexpected side effect (even if only suspected)
What are the top reported drug for unexpected side effects in Scotland?
Meningococcal B vaccines
Apixaban
Warfarin
Rivaroxaban
